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S. Tomoyasu, T. Nakanishi-Ueda, Y. Saito, T. Ueda, Y. Hasebe-Takenaka, H. Yasuhara, R. Koide, S. A. Mousa; Effect of the Superoxide Dismutase and Catalase Mimetic EDU on Oxygen-Induced Retinal Neovascularization in the Neonatal Rat. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3876.
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EDU (N-[2-(2-oxo-1-imidazolidinyl) ethyl]-N-phenylurea) is a superoxide dismutase (SOD) and catalase mimetic, with a potent cytoprotective effects against oxygen free radicals mediated cell injury and cell stress. EDU demonstrated potent inhibitory efficacy of oxidative stress and growth factors-induced angiogenesis in the chick chorioallantoic membrane model. Hence, the present study investigated the effect of EDU on oxygen-induced retinal neovascularization in neonatal rat model.
Oxygen-induced retinopathy (OIR) was induced by maintaining Sprague-Dawley neonatal rats in daily cycles of 80% oxygen (20.5 h), ambient air (0.5 h), and progressive return to 80%oxygen (3 h) for 12 days (P12). The rats were treated once daily with intraperitoneal injection of EDU (30mg/kg body weight),or distilled water (DW) from P6 to P17. On P12, P13 and P18, the rats were sacrificed and the retinal tissues were collected. At P18, the retinal neovascularization (NV) was scored and avascular areas of total retinal area (%AVA) were measured in ADPase stained retinas. The retinal vascular endothelial growth factor (VEGF) levels were measured by an immunoassay kit (R&D, MN, USA) at P12, P13 and P18.
The NV scores decreased in the EDU treated group (7.2±3.7, n=6) compared to the DW group (9.8±1.0, n=6). The %AVA in the EDU treated group (19±6%, n=6, P<0.01) were lower than those in the DW group (44±7%, n=6). The concentrations of VEGF in retina from untreated versus EDU treatment did not differ significantly as shown in Table below.Table: VEGF concentration (pg/mg protein) in rat retina
These results suggest that EDU treatment suppress the %AVA, with an increase in normal retinal vascular growth and decrease in retinal neovascularization. These EDU-mediated effects on avascular area and neovascularization scores are not related to VEGF production in retina.
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